Osteoporosis detection and treatment

1
Osteoporosis detection and treatment

• Dr Gill Coombes
• November 2007

2
Osteoporosis Definition (NIH, 2001)

• A skeletal disorder characterised by compromised
  bone strength predisposing a person to an
  increased risk of fracture. Bone strength
  primarily reflects integration of bone density
  and bone quality.

3
Development of osteoporotic bone
Rizzoli R ed In Atlas of Postmenopausal
Osteoporosis (1st edition) Science Press, 2004
4
Age and Osteoporotic Fractures
4,000 3,000 2,000 1,000
Men
Women
Hip
Hip
Vertebrae
Incidence/100,000 person-years
Vertebrae
Colles'
Colles'
3539
gt85
gt85
Age group, year
Cooper C. Epidemiology of Osteoporosis. Chapter
49IV. Metabolic Bone Diseases. Am Soc for Bone
Min Research 2003.
5
Osteoporosis Some facts and figures

• 1 in 2 women and 1 in 5 men aged 50 will suffer a
  fragility fracture in their remaining lifetime
• There are 20 million people aged 50 years and
  over in the UK. By 2020 this will have increased
  to 25 million.
• The lifetime risk of fracture in women at age 50
  is greater than the risk of breast cancer or
  cardiovascular disease

6
Annual Incidence of Osteoporotic fractures in
England and Wales

• 180,000 Symptomatic osteoporotic fractures
• 70,000 Hip fractures
• 25,000 Vertebral fractures
• 41,000 Wrist fractures
• Estimated total cost of treating osteoporotic
  fractures in postmenopausal women
• 1.5 to 1.8 billion in 2000
• 2.1 billion in 2010

7
Risk of subsequent fracture after initial
vertebral fracture
100 80 60 40 20 0
Cumulative incidence ()
0
1
2
3
4
5
6
7
8
9
10
Years following vertebral fracture
Melton LJ 3rd, et al. Osteoporos Int. 1999
10(3) 21421.
8
Management of Osteoporosis Identifying Risk
Factors for Osteoporosis

• Previous fragility fracture
• Corticosteroid use gt 3 months
• Family history, especially maternal hip fracture
• Medical conditions associated with osteoporosis
  e.g. RA, coeliac disease, hyperparathyroidism
• Premature menopause lt 45 years old
• Excess alcohol consumption
• Low BMI (lt19)
• Smoking

9
Bone density referral guidelines

• REASON FOR REFERRAL
• Corticosteroid therapy any dose for more than
  three months. However, patients of any age who
  have had a minimal trauma fracture or patients
  gt65 treat without a scan.
• Minimal trauma fracture eg wrist, vertebra,
  hip, pelvis. If known vertebral fracture, please
  state which vertebra.
• Early menopause before 45 years, or prolonged
  amenorrhoea gt 1 year scan when patient reaches
  50 years of age.
• Other diseases or treatments associated with
  osteoporosis
• Please specify ..
• Family History of osteoporosis in first degree
  relative, particularly maternal hip fracture.
• Significant radiological osteopenia
• Patients with proven osteoporosis who discontinue
  HRT and who are not on other OP treatment. Scan
  12 months after stopping

10
Osteoporosis and cancer treatments

• Prostate cancer
• Gonadorelin analogues

• Breast cancer
• Chemotherapy induced menopause
• Tamoxifen in
• pre-menopausal women
• Aromatase inhibitors

11
Osteoporosis and aromatase inhibitors

• All aromatase inhibitors cause bone loss
• (anastrazole, letrozole and exemestane)
• and are associated with increased fracture risk
• Bone loss is most rapid in the first 6-12 months
  (approx 3) after changing from tamoxifen
• Bone loss then slows eg 4-5 overall at 2 years
• Consider DXA scan at time of switching from
  tamoxifen to aromatase inhibitor especially if
  other risk factors present

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Lumbar Spine DXA Results
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DXA Results
15
Peripheral measurements

• Forearm DXA
• Heel DXA
• Heel ultrasound

16
Ten year probability of fracture age and BMD
Age (yrs) T-score
1 0 -1 -2 -3
-4
50 2.4 3.8 5.9 9.2 14.1 21.3 60 3.2
5.1 8.2 13.0 20.2 30.6 70 4.3
7.1 11.5 18.3 28.4 42.3 80 4.6 7.7 12.7
20.5 31.8 46.4
Kanis et al. Osteoporosis Int 2001 12 989-95.
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Kanis JA, Johnell O, Oden A et al. Ten year
probabilities of osteoporotic fractures according
to BMD and diagnostic thresholds. Osteoporos Int
2001 12989995.
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Management of OsteoporosisIdentifying Risk
Factors for Falling

• Medical conditions
• e.g. arrhythmias, postural hypotension
• Failing vision
• Sedative drugs
• Physical environment

19
Osteoporotic vertebral fractures
20
Investigation of osteoporosis

• FBC PV
• Igs / electrophoresis BJP
• TT glutaminase
• Biochemical screen including calcium
• TFTs
• Testosterone levels in men
• ? Vitamin D levels

21
Age-related changes in bone mass
Attainment of peak bone mass
Consolidation
Age-related bone loss
Menopause
Bone mass
Men
Fracture threshold
Women
0 10
20 30
40 50
60
Age (years)
Compston JE. Clin Endocrinol 1990 33 653682.
22
Management of Osteoporosis Lifestyle Measures
23
Treatment Options in Osteoporosis

• Antiresorptive drugs
• HRT
• Bisphosphonates
• etidronate
• alendronate
• risedronate
• ibandronate
• SERMs
• raloxifene
• Calcitonin
• Anabolic drugs
• PTH (teriparatide)

• Dual Action Bone Agents (DABAs)
• Strontium ranelate

24
New Treatment Options in Osteoporosis

• Antiresorptive drugs
• HRT
• Bisphosphonates
• etidronate
• alendronate
• risedronate
• ibandronate
• zoledronate
• SERMs
• raloxifene
• Calcitonin
• Anabolic drugs
• PTH analogues
• Forsteo (teriparatide)
• Preotact

• Dual Action Bone Agents (DABAs)
• Strontium ranelate

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Bone remodelling cycle
Pre-osteoblasts
Monocytes
Osteoblasts
Osteoclasts
Osteocytes
Servier Medical Art
26
Effect of alendronate on risk of fractures
RR 0.53 ( 95 Cl 0.41 0.68 )
18
16
14
12
Patients with new fractures after 3 years of
treatment ()
10
8
RR 0.52 ( 95 Cl 0.31 0.87 )
6
RR 0.49 ( 95 Cl 0.23 0.99 )
4
2
0
Vertebral fractures (p0.001)
Wrist fractures (p0.05)
Hip fracture (p0.05)
Adapted from Rizzoli. R Atlas of Osteoporosis.
(Second Edition). Curr Med Group 2005.
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Effect of risedronate on incidence of new
vertebral and non-vertebral fractures
RR 0.67 ( 95 Cl 0.44-1.04)
RR 0.51 ( 95 Cl 0.36 0.73 )
34
18
32
16
28
14
RR 0.61 ( 95 Cl 0.39 0.94 )
RR 0.59 ( 95 Cl 0.43 0.82 )
24
12
20
10
Incidence of new vertebral fractures ()
Incidence of new non-vertebral fractures ()
16
8
12
6
8
4
4
2
0
0
Vert-MN Years 0-3 Plt0.001
Vert-NA Years 0-3 Plt0.003
Vert-MN Years 0-3 NS
Vert-NA Years 0-3 P0.02
Vert-MN results adapted from Reginster, J.-Y.,
Minne, H.W. et al.Osteoporosis International
2000 11.83-91.Vert-NA results adapted from
Harris ST, Watts NB, Genant HK et al. JAMA 1999
282 13441352.
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Effect of ibandronate on incidence of vertebral
fractures
12
RR 0.50 ( 95 Cl 0.34 0.74)
10
RR 0.38 ( 95 Cl 0.25 0.59)
8


RR 0.44 ( 95 Cl 0.26 0.73 )
Fracture incidence ()
6
RR 0.39 ( 95 Cl 0.23 0.67 )

RR 0.42 ( 95 Cl 0.17 1.02 )
4

2
0
Year 1
Year 2
Year 3
plt0.001 versus placbo plt0.0017 versus placbo
Adapted from Rizzoli. R Atlas of Osteoporosis.
(Second Edition). Curr Med Group 2005.Reproduced
with permission from Chestnut CH 3rd, Skag A,
Christiansen C J Bone Miner Res 2004
191241-1249.
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Strontium has a dual action
FORMATION
RESORPTION

Strontium

Pre-OB
Pre-OC
REPLICATION

Strontium
DIFFERENTIATION
OB
OB
OB
Strontium
OC
BONE FORMING ACTIVITY
BONE RESORBING ACTIVITY
Bone
Ref 2 Marie PJ et al. Calcif Tissue Int.
200169121-129.
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Strontium increases bone mineral density
plt0.001
1 mean relative change from baseline versus
placebo (plt0.001)
Meunier P J et al. N Engl J Med. 2004
350459-468.
31
Strontium reduces the risk of vertebral fracture
(SOTI)

- 41
Patients ()
NNT 9

- 49
0-3 years
First year
Meunier P J et al. N Engl J Med. 2004
350459-468.
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Strontium ranelate reduces non-vertebral fracture
risk (TROPOS)
19
p0.031
12
10
8
patients with OP-related major non-vertebral
fractures over 3 years
95 Cl 0.66-0.98
6
4
2
0
Placebo
Strontium ranelate
n2537
n2555
1. Reginster JY, Seeman E, De Vernejoul MC, et
al. J Clin Endocrinol Metab 2005 90(5)
2816-2822. 2. Reginster JY, Hoszowski K, Roces
Varela A et al. Bone 2003 32(5) S94.
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Strontium ranelate reduces hip fracture in
patients at higher risk (gt 74 yr-old and T-score
lt-2.4) TROPOS
36
n1977
8
Strontium ranelate 2 g/day
7
n982
6
Placebo
n995
5

Patients ()
4
3
2
1
0
0-3 years
ITT, over 3 years RR 0.64 95 CI 0.412
0.997 p 0.046
1. Reginster JY, Seeman E, De Vernejoul MC, et
al. J Clin Endocrinol Metab 2005 90(5)2816-2822.
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NICE guidelines - Teriparatide

• Secondary prevention of osteoporotic
• fragility fractures in women aged 65 year and
  over who have had an unsatisfactory response to
  bisphosphonates and
• Have an extremely low BMD (T score -4) or
• Have a very low BMD (T score -3) with more than
  2 fractures plus 1 or more additional age
  independent risk factor

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